The interaction between glycolysis and glutaminolysis is mainly determined by two factors:
- the existence of a residual active glycerol 3-phosphate shuttle.
- the asscociation of PGM within the glycolytic enzyme complex.
In tumor cells cytosolic hydrogen is transported into the mitochondria via two different shuttle systems: the malate-aspartate-shuttle and the glycerol 3-phosphate shuttle.
The malate-aspartate-shuttle is part of the glutaminolytic pathway.
The glycerol 3-phosphate shuttle depends on the expression of cytosolic glycerol 3-phosphate.
In cells without cytosolic glycerol 3-phosphate dehydrogenase activity, such as MCF-7 cells, transformed oval cells and transformed NIH 3T3 cells the glycerol 3-phosphate shuttle is inactive and glutamine consumption increases with increasing glucose consumption.
In the absence of an active glycerol 3-phosphate shuttle the intensity of the interaction between glycolysis and glutaminolysis depends on the association of PGM inside the glycolytic enzyme complex.
When PGM is associated inside the glycolytic enzyme complex glycerate 3-phosphate is converted to pyruvate and the nitrogen of glutamine is transferred to pyruvate and excreted as alanine. In these cells only a weak correlation between the glycolytic and glutaminolytic flux rate is detectable.
When PGM is not associated within the glycolytic enzyme complex glycerate 3-phosphate is channeled in serine synthesis. For serine synthesis from glycerate 3-phosphate, glutamate is necessary as donor of the amino group. Glutamate is a degradation product of glutamine. Consequently, in cells with PGM not associated within the glycolytic enzyme complex a strong correlation between the glycolytic and glutaminolytic flux rates occurs.